While there are several well-known similarities between SIV and HIV-1 and the disease syndromes in the respective hosts, the need for an HIV-1 model remains critical to understanding HIV-1 pathogenesis. Interest in the search for an HIV-1 model has been renewed with recent reports describing HIV-SIV chimera and HIV-1 infections in macaques. This project will explore the susceptibility of Japanese, rhesus, and pig- tailed macaques to laboratory strains of HIV-1 and the potential for adapting laboratory and patIent isolates of HIV-1 to susceptible species. We proposed the following studies, aimed at establishing HIV-1 infection in macaques: i) determine the relative susceptibility of Japanese, rhesus, and pig-tailed macaque peripheral blood mononuclear cells (PBMC) to HIV-1 infectIon in vitro, ii) identify new HIV-1 isolates that replicate in PBMC from susceptible species in vitro that may be good candidates for in vivo infections, iii) promote adaption of HIV-1 to susceptible macaque species via serial passage in vitro and in vivo, and iv) construct env recombinant clones HIV-1 competent to replicate in macaque PBMC in vitro. The long-term goal of this project is to establish a macaque model of HIV- 1 infection and determine molecular changes in the virus env gene that accompany species adaptation.